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2 mars 2023
- handle: 10670/1.hbty6p
- Leduc-Gaudet, Jean-Philippe; Franco-Romero, Anais; Cefis, Marina; Moamer, Alaa; Broering, Felipe E.; Milan, Giulia; Sartori, Roberta; Chaffer, Tomer Jordi; Dulac, Maude; Marcangeli, Vincent; Mayaki, Dominique; Huck, Laurent; Shams, Anwar; Morais, José A.; Duchesne, Élise; Lochmuller, Hanns; Sandri, Marco; Hussain, Sabah et Gouspillou, Gilles (2023). « MYTHO is a novel regulator of skeletal muscle autophagy and integrity ». Nature Communications, 14(1199).
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http://archipel.uqam.ca/16396/
Ce document est lié à :
https://www.nature.com/articles/s41467-023-36817-1
Mots-clés
skeletal muscle mass autophagy protein synthesis muscle atrophy muscle hypertrophy myopathy tubular aggregates myotonic dystrophy type 1 mTORC1Sujets proches
Muscle Musculature Myodynamics MyologyCiter ce document
Jean-Philippe Leduc-Gaudet et al., « MYTHO is a novel regulator of skeletal muscle autophagy and integrity », UQAM Archipel : articles scientifiques, ID : 10670/1.hbty6p
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Résumé
Autophagy is a critical process in the regulation of muscle mass, function and integrity. The molecular mechanisms regulating autophagy are complex and still partly understood. Here, we identify and characterize a novel FoxO-dependent gene, d230025d16rik which we named Mytho (Macroautophagy and YouTH Optimizer), as a regulator of autophagy and skeletal muscle integrity in vivo. Mytho is significantly up-regulated in various mouse models of skeletal muscle atrophy. Short term depletion of MYTHO in mice attenuates muscle atrophy caused by fasting, denervation, cancer cachexia and sepsis. While MYTHO overexpression is sufficient to trigger muscle atrophy, MYTHO knockdown results in a progressive increase in muscle mass associated with a sustained activation of the mTORC1 signaling pathway. Prolonged MYTHO knockdown is associated with severe myopathic features, including impaired autophagy, muscle weakness, myofiber degeneration, and extensive ultrastructural defects, such as accumulation of autophagic vacuoles and tubular aggregates. Inhibition of the mTORC1 signaling pathway in mice using rapamycin treatment attenuates the myopathic phenotype triggered by MYTHO knockdown. Skeletal muscles from human patients diagnosed with myotonic dystrophy type 1 (DM1) display reduced Mytho expression, activation of the mTORC1 signaling pathway and impaired autophagy, raising the possibility that low Mytho expression might contribute to the progression of the disease. We conclude that MYTHO is a key regulator of muscle autophagy and integrity.